The objective of this proposed research is to define the pharmacokinetics of prednisone and prednisolone after oral and intravenous dosing in kidney transplant patients routinely receiving the drug. We want to determine the relationships between the dose, bioavailability, plasma clearance, half-life, volume of distribution and plasma protein binding of prednisolone, with measures of efficacy such as alteration of lymphocyte function and corticosteroid-induced side effects such as cushingoid features. We plan to determine factors which could account for interindividual differences in the bioavailability or elimination of prednisone/prednisolone in kidney transplant patients. These would include such factors as antacids, food, other drugs (phenytoin, phenobarbital, azathioprine) kidney rejection, and the influence of hemodialysis. For these studies we will utilize a specific and sensitive HPLC assay which was developed and is currently used at UCSF. This assay will allow us to measure prednisolone, prednisone, cortisol and cortisone simultaneously in the plasma of kidney transplant patients. These studies should provide a great deal of information on the pharmacokinetics and pharmacodynamics of prednisone/prednisolone in kidney transplant patients. This would then provide a more rational basis for dosing prednisone in these patients, thereby minimizing side effects while attaining maximal immunosuppressive effects.